I. Neuromodulation Stimulation
Neuromodulation stimulation (the electrical excitation of nerves to indirectly affect the stability or performance of a physiological system) can provide functional and/or therapeutic outcomes. While existing systems and methods can provide remarkable benefits to individuals requiring neuromodulation stimulation, many limitations and issues still remain. For example, existing systems can often require the user to wear an external stimulator, which may provide a positive functional outcome, but may also negatively affect quality of life issues.
A variety of products and treatment methods are available for neuromodulation stimulation. As an example, neuromodulation stimulation has been used for the treatment of sexual dysfunction, which affects both men and women. A wide range of options exist for the restoration of sexual function. Treatments include everything from medications, simple mechanical devices, psychological counseling, external stimulators, and surgically implanted devices.
Both external and implantable devices have been described in the art for the purpose of neuromodulation stimulation for the restoration of sexual function. The operation of these devices typically includes the use of an electrode placed either on the external surface of the skin or a surgically implanted electrode. Although these modalities have shown the ability to provide a neuromodulation stimulation with some positive effects, they have received limited acceptance by patients because of their limitations of portability, limitations of treatment regimes, and limitations of ease of use and user control.
II. Sexual Dysfunction
One form of male sexual dysfunction is know as Erectile Dysfunction (ED), and is often referred to as “impotency.” There are some common diseases such as diabetes, Peyronie's disease, heart disease, and prostate cancer that are associated with impotency or have treatments that may cause impotency. And in some cases the cause may be psychological.
Erectile Dysfunction is common problem affecting men and is defined as the inability to achieve or maintain a penile erection sufficient for sexual activity. It is estimated that 35% to 50% of all men aged 40 to 70 have some form of ED, nearly 46 million Americans have ED, and over 150 million men have ED worldwide. It is also estimated that sexual dysfunctions occur in 43 percent of women in the United States. It would cost $3.5 billion per year if only one fifth of Americans with ED were treated with the first line of treatment (oral therapy such as PDE-5 inhibitors), and the cost for the second line of treatment (such as injection or transurethral administration of alprostadil) is approximately twice as expensive. A cost-effective therapy is needed because the number of men seeking treatment tripled between 1997 and 2000 and is expected to increase as awareness of treatment options for ED becomes more widespread.
The severity of erectile dysfunction can range from 1) mild ED, in which a man is occasionally unable to achieve and sustain an erection sufficient for intercourse, to 2) frequent or moderate ED to 3) severe or complete ED, in which a man is never able to produce and sustain an erection sufficient for intercourse. The prevalence of moderate to complete ED increases with age. Approximately 20% of men aged 40 years have moderate to severe ED and approximately 70% of men aged 70 years have moderate to severe ED. Over 70% of men with ED report that their quality of life is moderately to severely reduced by ED, and over 70% of men with ED feel hurt by the response of their partner to their ED and feel “to some extent a failure” because of their ED. Thus, ED is often associated with poor self-image, depression, and it can affect interpersonal relationships and lead to increased mental stress.
ED is often a result of a combination of psychological and organic factors, but it is thought to be purely psychological in origin in less than 30% of the cases. Organic factors can include complications from neurologic diseases (stroke, multiple sclerosis, Alzheimer's disease, brain or spinal tumors), chronic renal failure, prostate cancer, diabetes, trauma, surgery, medications, and abnormal structure. However, most cases of ED are associated with vascular diseases. An erection cannot be sustained without sufficient blood flow into and entrapment within the erectile bodies of the penis, and vascular related ED can be due to a malfunction of either the arterial or the venous system.
In a healthy individual, increased blood low into the penis by means of arterial dilation and decreased blood flow from the penis via venous occlusion generates penile erection. Activation of a parasympathetic nerve such as the cavernous nerve, which causes relaxation of corporeal smooth muscle of the cavernosal and trabecular spaces, generates the arterial dilation. A normal reflex penile erection begins with the filling and expansion of the three erectile bodies: the corpus spongiosum and the two corpora cavernosa. This expansion compresses the venules against the tunica albuginea, preventing blood from leaving the penis and furthering the erection by way of intrinsic venous occlusion (within the penis). Extrinsic venous occlusion (outside the penis) is provided by activation of a somatic nerve such as the pudendal nerve, which causes contraction of the bulbospongiosus and ischiocavernosus muscles, trapping the blood in the penis erectile tissues and increasing tumescence (Schmidt and Schmidt, Sleep 1993; 16:171-183).
Persons with vasculogenic erectile dysfunction are unable to achieve penile erection due to either insufficient arterial blood flow or insufficient venous occlusion or both. Normal reflex erection coordinates dilation of penile blood vessels, augmenting vascular filling, and venous occlusion, preventing leakage and increasing penile stiffness.
In animal studies, it has been found that stimulation of the cavernous nerve (referenced as target nerve A) resulted in an increase of intracavernous pressure, and additional stimulation of the pudendal nerve (referenced as target nerve B) increased the intracavernous pressure to well above the systolic pressure, producing a reflex erection (see FIG. 1).
FIGS. 2 and 3 show a profile and cross-section of the penis, illustrating the anatomical relationship of the erectile tissue (corpora cavernosa and corpus spongiosum) inside the penis. FIGS. 4 and 5 show the physiological changes in the size of the penile arteries, erectile tissue, and veins during erection. FIG. 4 shows the penile arteries constricted, the erectile tissue collapsed, and the veins open prior to an erection. Arterial dilation leads to increased inflow of blood, which fills and expands the erectile tissue as the veins are compressed to decrease outflow of blood from the erectile tissue, as shown in FIG. 5.
III. Methods of Treatment For ED
Methods of treatment for erectile dysfunction are available but are either often discontinued due to loss of efficacy or side effects or reserved as a final recourse requiring irrevocable damage. Currently three lines of treatment exist for ED. Oral therapy (PDE-5 inhibitors) is usually the first line of treatment, and it can be effective in up to 70% of men when it is first administered, but half of the patients stop taking PDE-5 inhibitors because they lose their effectiveness within one to three years.
The second line of treatment is usually a minimally invasive therapy such as a vacuum device or direct administration of a vasoactive agent. The second-line treatments are usually effective in 33% to 70% of men, but they are also later discontinued by over half of the patients, often due to side effects such as pain or local damage at the site of administration. For the 30% to 65% of men who fail or discontinue oral therapy, the total cost for the second line of treatment (vacuum device or alprostadil, administered via injection or transurethrally) would be $1 to $6 billion. However, side effects of pain and local damage are associated with the second line of treatment, and at least half of the men discontinue this form of therapy.
If the men who failed or discontinued both the first and second lines of treatment chose to receive a penile prosthesis (the third line of treatment), the total cost would be over $20 billion. Yet, implantation of a penile prosthesis is reserved for the final method of treatment because the implantation causes permanent (irrevocable) damage to the erectile tissue resulting in the loss of any future erection if the implant is removed. Thus, an alternative approach is needed that can provide a multitude of advantages over the current therapies.
IV. Neuromodulation Stimulation
Neuromodulation stimulation provides a multitude of advantages over the three previously described forms of erectile dysfunction treatment. Systemic side effects (headache, flushing, dyspepsia, etc.) and permanent damage to the corpora cavernosa may be avoided by electrically stimulating one or more peripheral nerves to coordinate arterial dilation with venous occlusion, producing an erection.
An implantable stimulation system is needed that can provide an erection quickly and is acceptable to men who use or may need to use nitrates to treat cardiovascular disease because over 35% of men with cardiovascular disease develop ED. The loss of efficacy of oral therapy is likely due to the long duration (four to eighteen hours) of action, and the consistently elevated drug concentrations can reduce the response to the drug via tachyphylaxis or increased tolerance as seen with nitroglycerin tolerance. No loss of efficacy is expected with an implantable stimulation system that is adapted to be activated only minutes before (e.g., two to ten) and during erection, and it will provide controlled release of neurotransmitter via activation of targeted peripheral nerves.
The implantable stimulation system may be activated by the movement of a magnet over a magnetic reed switch within an implantable pulse generator of the stimulation system, or the press of a remote button, for example. Unlike the second line of treatment, this approach will not require a constrictive ring, needle insertion, or urethral-suppository insertion, which can cause local injury prior to each erection and lead to discontinuation of treatment. In contrast to the penile implant, an implantable stimulation system approach will not damage the erectile tissue.
There remains a need for systems and methods that can effectively restore sexual function, in a straightforward manner, without requiring drug therapy and complicated (and in some instanced irrevocable) surgical procedures.